Introduction

Coronavirus disease (COVID-19) has spread worldwide since December 2019, and the first patient in Japan was confirmed in January 20201. Recent studies have shown that the COVID-19 pandemic was associated with fewer new diagnoses of several cancer types per month in various countries2,3,4,5,6,7,8,9. Particularly, cancers such as gastrointestinal, oral, and head and neck cancers were more susceptible to the reduction in screenings due to the COVID-19 pandemic, raising concerns about detection at more advanced stages10,11,12. In Japan, the pandemic has led to the postponement or cancellation of cancer screening13,14,15,16, delays in medical consultations, and an increase in the number of gastrointestinal cancers diagnosed as advanced17.

Regarding bone and soft tissue sarcomas, several reports also have shown the negative impact on patient’s diagnosis by the COVID-19 pandemic. The time from the first symptom to definitive histological diagnosis in patients with soft tissue sarcoma was delayed during the pandemic in Italy18. Furthermore, a study in Poland showed that the pandemic caused delays in performing biopsies of bone tumors19. However, there has been no report from Japan or other Asia countries regarding the impact of the COVID-19 pandemic on sarcoma patients.

During the COVID-19 pandemic, the government of the Fukuoka area in Japan declared a state of emergency to ask people to refrain from going out. It is unknown whether the emergency declaration, in a non-punitive manner, affected the consultation behavior of sarcoma patients during the COVID-19 pandemic.

The primary purpose of this study was to determine the impact of the COVID-19 pandemic on the consultation behavior of patients with bone and soft tissue sarcoma and its effect on the clinical stage at diagnosis. We also investigated the impact of the local government’s emergency declaration on the diagnosis of sarcomas through a collaboration among three major sarcoma treatment facilities in the Fukuoka area.

Results

A total of 403 new patients with bone and soft tissue sarcoma visited one of our hospitals between January 2018 and December 2021. Table 1 shows the number of new patients with bone and soft tissue sarcoma per month before and during the COVID-19 pandemic. Compared with before the COVID-19 pandemic, we did not observe a significant reduction in the number of overall new patients per month by 10% and in those of primary new patients by 15% during the COVID-19 pandemic, respectively. The number of new soft tissue sarcoma patients per month significantly decreased from 6.0 before the COVID pandemic to 4.5 during the COVID-19 pandemic (adjusted RR, 0.75; 95% confidence interval [CI] 0.58–0.96; p = 0.02), while there was no significant difference in the number of patients with bone sarcoma.

Table 1 The number of new patients with bone and soft tissue sarcoma per month before and during COVID-19 pandemic.
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Next, we examined the trends in the number of patients with bone and soft tissue sarcoma during the COVID-19 pandemic in more detail, focusing on the state of emergency declaration. The relative number of new patients with bone and soft tissue sarcoma during the COVID-19 pandemic is shown in Fig. 1, with the number of new patients before the COVID-19 pandemic set at 100. The number of new patients tended to be lower overall during the periods of state of emergency, highlighted by several colors. The number of new patients per month was aggregated for the five state-of-emergency periods and is summarized in Table 2. The monthly numbers of total new patients, newly diagnosed cases of primary patients not treated elsewhere, and those of primary soft tissue sarcoma were decreased significantly during states of emergency (p = 0.01, < 0.001, and 0.001, respectively) compared to before the COVID-19 pandemic.

Fig. 1
figure 1

Relative change in new bone and soft tissue sarcoma patients. Color-shaded areas refer to the state of emergency period. The number in the figure indicates a relative number of new patients when before the COVID-19 pandemic was set at 100.

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Table 2 The number of new patients with bone and soft tissue sarcoma per month before COVID-19 pandemic and during states of emergency.
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Regarding the clinical stage of the primary soft tissue sarcoma patients, the proportion of stage IV patients was significantly higher during the COVID-19 pandemic (9% vs. 18%, p = 0.04) (Table 3 and Fig. 2). Regarding the other clinical characteristics, including age, location, and tumor size, there was no significant difference between before and during the COVID-19 pandemic.

Table 3 The characteristics of primary (untreated elsewhere) soft tissue sarcoma patients before and during COVID-19 pandemic.
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Fig. 2
figure 2

Proportion of clinical stages of primary soft tissue sarcoma patients before and during the coronavirus disease pandemic.

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Figure 3 shows the proportion of sarcoma patients divided by the length from the onset of symptoms to the initial visit to a physician. For bone and soft tissue tumors, the proportion of patients who had their first visit within one month tended to be lower in the COVID-19 pandemic phase. However, there were no statistically significant differences. Regarding the interval from the initial visit to a physician to referral visit to specialist hospitals, the proportion of bone sarcoma patients who visited specialist hospitals within one month from the initial visit significantly increased during the pandemic (50 vs. 78%), as shown in Fig. 4.

Fig. 3
figure 3

Proportion of sarcoma patients per each interval length from the onset of symptoms to the initial visit to a physician.

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Fig. 4
figure 4

Proportion of sarcoma patients per each interval length from the initial visit to a physician to referral visit to specialist hospitals.

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Discussion

This study investigated the impact of the COVID-19 pandemic and a state of emergency declaration on the consultation behavior of patients with bone and soft tissue sarcoma. In Japan, the first case of COVID-19 was reported in January 2020, and many medical facilities postponed nonurgent surgeries and cancer screening after March 2020, when the World Health Organization declared a pandemic. Furthermore, in the Fukuoka area, the government declared a state of emergency five times in response to the outbreak of COVID-19 infection and restricted people from leaving their homes unnecessarily.

Using a Poisson regression model, we evaluated the changes in the number of new patients per month between before and during the COVID-19 pandemic or the period of a state of emergency declaration. During the COVID-19 pandemic, the overall number of new patients per month decreased by 10%, and the number of primary patients decreased by 15%, but these differences were not statistically significant. A retrospective study using the national registry in Japan showed a substantial reduction of 12% in the diagnoses of gastric cancer, 11.5% in prostate cancer, and 8.3% in colon cancer during the COVID-19 pandemic20. The reduction rates were similar to those of other cancer types, but the lack of statistical significance might be due to the small samples. On the other hand, we observed a significant reduction in the numbers of overall new patients per month during the state of emergency by 32% and in those of primary new patients by 44% compared with before the COVID-19 pandemic, respectively. A substantial reduction in the number of new patients was observed during all five states of emergency, and a rebound was noted in the periods after the state of emergency declaration, as clearly shown in Fig. 1. The study on healthcare service use in Japan revealed that overall outpatient visits declined by 22% in May 2020, during the first state of emergency in Japan, with a decrease of 25% observed in orthopedics21. In our study, the number of new primary patients declined significantly by 43% during the same period and by 54% from August to October 2020. These results suggest that the state of emergency in Japan during the COVID-19 pandemic likely significantly impacted the decrease in the number of new patients with bone and soft tissue sarcoma.

We observed a significant reduction in the number of new patients with soft tissue sarcoma by 25% during the COVID-19 pandemic (6.0 vs. 4.5; p = 0.02) and by 45% during the state of emergency (6.0 vs. 3.3; p = 0.001) but did not observe the same trend in those with bone sarcoma during both periods. These results are consistent with the retrospective study in Italy involving 372 patients with soft tissue sarcoma that showed a significant reduction in the number of first visits and new diagnoses during March–May 2020 in the COVID group compared to the control group18. Moreover, a report in Poland involving 87 patients with bone tumors revealed that the pandemic resulted in delays in performing biopsies but did not affect the number of new diagnoses19. The discrepancy in diagnosis trends may be attributed to differences in the development and progression patterns between bone-derived and soft tissue-derived sarcomas. In general, patients with bone sarcomas often present pain due to increased pressure within the bone tissue caused by the expanding tumor mass in the limited space of the bone. Conversely, the initial symptom of patients with soft tissue sarcoma is frequently lump without pain. According to the descriptions on medical records about subjective symptoms related to the presence or absence of pain at the first visit, nearly 80% of patients with bone sarcoma present with pain, whereas only about 30% of patients with soft tissue sarcoma (data not shown). It is plausible that patients with painless lumps may have avoided consultation due to the fear of COVID-19 infection rather than seeking treatment for their symptoms.

In literature, some studies investigated whether the COVID-19 pandemic caused delays in cancer diagnosis, with varying results. In lung cancer, a report did not show delays in diagnosis or treatment initiation during the COVID-19 pandemic22. In contrast, a study reported delays in treatment due to the onset of the pandemic in breast cancer23. We observed that the proportion of patients who were seen first within one month from the onset of symptoms was decreased during the pandemic for bone sarcoma (46 vs. 39%, respectively) and soft tissue sarcoma (37 vs. 32%, respectively), but these differences were not statistically significant. On the other hand, the proportion of bone sarcoma patients who saw specialist hospitals within one month from the initial visit significantly increased during the pandemic (50 vs. 78%, respectively), and the proportion of those who took one to three months significantly decreased (38 vs. 11%, respectively). These results are similar to the study’s findings in Poland19. Daniel et al. reported that the median patient-related delay for patients with bone sarcoma was increased from 1 to 2 months during the pandemic, and the doctor-related delay was decreased from 5 to 3 months. This trend may reflect the diversity of symptoms or the complexity of the process from initial consultation to sarcoma diagnosis. These findings suggest that the period from the onset of symptoms to the initial visit can be particularly delayed in sarcoma patients during a pandemic. Therefore, it is crucial for healthcare institutions to continuously disseminate information about sarcoma and encourage patients with any symptoms to see hospitals promptly.

Previous studies have evaluated whether the COVID-19 pandemic impacted the cancer stage at diagnosis. The Italian COVID-DELAY study showed that new patients with colorectal, breast, and lung cancer in 2020 were less likely to be diagnosed with early stage and more likely with later stage22,24,25. In Japan, the number of patients diagnosed with stage I gastric and colorectal cancers was significantly decreased, and that with stage III colorectal cancer increased17. In this study, we observed a similar rise in the proportion of stage IV patients during the COVID-19 pandemic. Although it is unclear whether such later-stage diagnosis will have a consequential impact on survival, previous studies show the clinically relevant association of delays in diagnosis and treatment with poor outcomes for a range of cancer types26,27,28,29,30 and soft tissue sarcoma31,32,33,34. One modeling study in England examined the impact of the COVID-19 pandemic on cancer survival and suggested that delays of several months in the treatment would lead to a substantial proportion of many patients with early-stage cancers progressing to the incurable stages35. A delay in the diagnosis of sarcoma is prone to occur due to its rarity and heterogeneity in presentation. Given the absence of screening tests for sarcoma and the context mentioned above, the COVID-19 pandemic may adversely affect patient prognosis.

The negative impact of COVID-19 has underscored the need for enhanced preparedness for future pandemics. It is crucial to understand and address the problems of sarcoma patients, such as their scarcity, diverse histological types, weakened immune system, necessity for diagnosis and treatment by specialists, or limited treatment strategies when the disease progresses with a flexible and comprehensive approach. This includes raising awareness of the disease, stringent infection prevention measures, using telemedicine, setting treatment priorities and optimal allocation of medical resources, and collaboration among multidisciplinary teams36,37,38. Through these measures, we can ensure a safe and effective diagnosis or treatment environment for sarcoma patients.

Our study has several limitations. First, we only collected data from three hospitals, which might have limited the power of analyses, although those three hospitals are major sarcoma-treatment hospitals in the Fukuoka area. More representative results on the impact of the COVID-19 pandemic on bone and soft tissue sarcoma can be provided by including a larger sample of patients from more institutions. Second, this study could not evaluate outcomes other than a clinical-stage, such as overall or disease-free survival. It would be necessary for future studies to assess whether or not the COVID-19 pandemic is associated with those clinical outcomes for bone and soft tissue sarcoma patients.

In conclusion, the COVID-19 pandemic negatively impacted the early consultation of soft tissue sarcoma patients, increasing the proportion of stage IV patients at initial diagnosis. Also, the government’s emergency declaration led to the withholding of consultations by patients with primary bone and soft tissue tumors.

Methods

Study design and outcomes

This study included all bone and soft tissue sarcoma patients who had initially visited our hospitals, including Kyushu University Hospital, Kyushu Rosai Hospital, and Kyushu Cancer Center, between January 2018 and December 2021. Patients with an inconclusive pathological diagnosis of sarcoma were excluded from this study. Of 403 bone and soft tissue sarcoma patients, 315 were primary (untreated elsewhere) patients. Our hospitals include major sarcoma treatment facilities located in the Fukuoka area, which has a population of approximately 4 million, on Kyushu Island, Japan. We retrospectively collected the following data from medical charts and related documents: date of initial consultation at one of our hospitals, age, sex, symptoms, interval from onset of symptoms to the initial visit to a physician, interval from the initial visit to a physician to referral visit to specialist hospitals, size of the tumor, location of the tumor, bone or soft tissue tumor, histological diagnosis, and clinical stage at diagnosis based on the American Joint Committee on Cancer (AJCC) staging system39. Intervals from the onset of symptoms to the initial visit to a physician and from the initial visit to a physician to referral visit to specialist hospitals were classified into three categories (less than one month, one to three months, and more than three months) based on the previous literature40. For the analysis of the data on the intervals, 292 patients were included, as we excluded 23 cases with missing data. This study was conducted following the principles of the Declaration of Helsinki. The study protocol was approved by the Kyushu University Hospital Institutional Review Board (approval number: 22316-00) and the chief executive of Kyushu Rosai Hospital and Kyushu Cancer Center, respectively, under the laws of Japan41. Informed consent was obtained in the form of opt-out on the web-site. No patients were excluded from this study through opt-out.

The period of the COVID-19 pandemic and a state of emergency in the Fukuoka area

World Health Organization (WHO) characterized the outbreak of COVID-19 as a pandemic on 11 March 2020. Since the COVID-19 pandemic in the Fukuoka area began in March 2020, the period before the COVID-19 pandemic was defined as January 2018 to February 2020, and that during the COVID-19 pandemic in Japan was defined as March 2020 to December 2021 in this study. Within the above period, a state of emergency in the Fukuoka area was declared by the prefectural governments for the following five periods; (1) April 7 to May 14, 2020, (2) August 5 to October 8, 2020, (3) December 12, 2020 to February 28, 2021, (4) May 12 to June 20, 2021, (5) July 28 to October 11, 2021. We normalized the average monthly number of patients before the COVID-19 pandemic to 100 and calculated each period's relative increase or decrease.

Statistical analysis

Continuous variables were compared using a t-test, and chi-square tests were used to compare the proportions of categorical variables between groups. The rate ratio (RR) was analyzed using a Poisson regression model. A p-value of less than 0.05 indicated a statistically significant difference. All statistical analyses were conducted using JMP statistical software version 16.0 (SAS Institute).